Association of the ACTN3 genotype and physical functioning with age in older adults

Matthew J. Delmonico, Joseph M. Zmuda, Brent C. Taylor, Jane A. Cauley, Tamara B. Harris, Todd M. Manini, Ann Schwartz, Rongling Li, Stephen M. Roth, Ben F. Hurley, Douglas C. Bauer, Robert E. Ferrell, Anne B. Newman

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Objective. The purpose of this study was to examine the association of the alpha-actinin-3 (ACTN3) R577X polymorphism on muscle function and physical performance in older adults. Methods. We measured knee extensor torque, midthigh muscle cross-sectional area, muscle quality, short physical performance battery score, and 400-meter walk time at baseline and after 5 years in white older adults aged 70-79 years in the Health, Aging and Body Composition Study cohort (n = 1367). Incident persistent lower extremity limitation (PLL) over 5 years was additionally assessed. We also examined white men in the Osteoporotic Fractures in Men Study, a longitudinal, observational cohort (n = 1152) of men 65 years old or older as a validation cohort for certain phenotypes. Results. There were no significant differences between genotype groups in men or women for adjusted baseline phenotypes. Male X-homozygotes had a significantly greater adjusted 5-year increase in their 400-meter walk time compared to R-homozygotes and heterozygotes (p = .03). In women, X-homozygotes had a ∼35% greater risk of incident PLL compared to R-homozygotes (hazard ratio = 0.65, 95% confidence interval = 0.44-0.94). There were no other significant associations between any of the phenotypes and ACTN3 genotype with aging in either cohort. Conclusions. The ACTN3 polymorphism may influence declines in certain measures of physical performance with aging in older white adults, based on longitudinal assessments. However, the influence of the ACTN3 R577X polymorphism does not appear to have a strong effect on skeletal muscle-related phenotypes based on the strength and consistency of the associations and lack of replication with regard to specific phenotypes.

Original languageEnglish (US)
Pages (from-to)1227-1234
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume63
Issue number11
DOIs
StatePublished - Nov 2008

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS The Health ABC study was supported by research contracts #1-AG-6-2101, #1-AG-6-2103, and #1-AG-6-2106 from the National Institute on Aging (NIA). This study was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), NIA. The MrOS Study is supported by NIH funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the NIA, the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. Additional support was also provided by NIAMS grants R01-AR051124, R01-AG021024, AG-022791, the NIA Aging Training Grant, and a grant from the Department of Epidemiology, University of Pittsburgh.

Keywords

  • Elderly
  • Genetics
  • Sarcopenia
  • Skeletal muscle

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